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53 Cards in this Set

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How would you manage Heparin induced thrombocytopenia?
Stop the heparin
What are the paradoxes associated with HIT?
Treat with blood thinner yet see blood clots
Lowered platelet count, expect bleeding disorder but still clotting disorder.
Simply stopping Heparin may not prevent blood clots
Platelets transfusions can worsen thrombosis
Do not switch to warfarin, as acute monotherapy
Activated platelets release this protein that binds to heparin
Platelet Factor 4 (PF4)
What is the initiation event in Heparin induced thrombocytopenia ?
Heparin-PF4 complex is seen as foreign by the body which then is bound by IgG. The Fc receptor binds more platelets and activates them and this is the start of a viscious cycle.
How are blood cells targeted for injury in a patient with Heparin induced thrombocytopenia?
The blood vessels have heparin-like molecules which bind to PF4, as it is being released in large amounts. IgG bind the complex and downstream of this is the injury of the blood vessels. Injured blood vessels + activated platelets --> recipie for disaster.
Why is HIT considered a thrombotic disease?
Thrombin amplifies and perpetuates HIT via the following:
Thrombin activates endothelial cells --> form cytokines and Tissue Factor
Thrombin activates monocytes --> form cytokines and Tissue Factor.
Thrombin activates platelets --> Platelet aggregation, release of granules & TXA2 synthesis. Activated platelets cause th release of more thrombin.
Thrombin activates the coagulation cascade:
Fibrinogen - Fibrin
Factor XIII - XIIIa
Amplification:
Factor VIII - VIIIa
Factor V - Va
Protein C
Where does Heparin come from?
Natural source: cow, lung, porcein intestine, heterogenous product that is sulfated. It is a polymer of variety of different lengths.
What patients/ clinical setting are patients more likely to get HIT?
Cardiac
Orthopedic
Intensive care
Name a clotting disorder in which can get clots in either venous or arteries
HIT
Clinical sequelae of HIT:
Another thrombus - 50%
Amputation - 21%
Death - 30%MI, stroke, occlusion of vital organ, primary embolus
What is the typical time period for the onset of HIT?
4 - 14 days, 90% of cases that occur.
Why might one have a rapid onset of HIT?
Previous exposure to Heparin.
Why might one have a delayed onset of HIT?
9 - 10 days after heparin stopped still have antibodies that are bound to heparin-like molecules on endothelial cells.
How do you diagnose HIT?
Fall of platelet count with the right timing with respect to starting the heparin <150,000.
Drop of platelets 30 - 50% from baseline even though not in the thrombocytopenic range, stressed people may have high amounts of platelets.
DO NOT DELAY TREATMENT, INITIATE RX BEFORE GETTING LABORATORY TEST BACK. THIS IS A CLINICAL Dx, LAB HELPS CONFIRM DIAGNOSIS.
Differential dx of thrombocytopenia in ICU?
Severe sepsis, DIC
Drugs - lower platelet count
Dilutional effect - due to blood transfusion
If have had blood go through extracorporeal circuit
What lab tests would you order to diagnose HIT?
Draw blood sample
Test antibody presence
ELISA test against Heparin and PF4
Test ab ability to activate platelets - load up platelets with radioactive serotonin and measure how much serotonin comes out.
Which test is the gold standard for diagnosis of HIT because of its specificity?
SRA (Serotonin Release Assay) -has 100% specificity. If positive, then can be certain that these antibodies are specific for HIT.
ELISA test - sensitive - used for its negative predictive value.
What kind of thrombocytopenia does this patient have? 50 - 150 0000
Mild thrombocytopenia
What kind of thrombocytopenia does this patient have? 20 -50,000

*** MAJORITY OF HIT PATIENTS ***
mild - moderate thrombocytopenia
What kind of thrombocytopenia does this patient have? <20,000
severe thrombocytopenia
How do you treat HIT?
CLINICAL SUSPISCION OR DIAGNOSIS OF HIT --> STOP ALL FORMS OF HEPARIN IMMEDIATMO --> STRONGLY CONSIDER ANTICOAGULATION W/ DTI (DIRECT THROMBIN INHIBITORS)--> CONFIRMATORY TESTS.
Name two bivalent DTI's that bind and block both the fibrinogen binding site and active site:
Bivalirudin
Lepirudin
DTI that blocks the active binding site only:
Argatroban
Name this drug is the recombinant for of Hirudin - an anticoagulant from saliva of leeches and was first drug approved for HIT:
Lepirudin
Half life of Lepirudin.
How is it excreted?
Excreted via kidney
Half life is 80 minutes, to have constant drug in the body with short half life, would give a continuous IV.
This drug is active site specific, indicated in prophylaxis and Rx of HIT, does not cross-react with heparin induced ab.
Argatroban
How is Argatroban eliminated?
Half life:
Liver
39-51 minutes.
Which drug needs care when switching over with coumadin (oral anticoagulant) because even though monitored with aPTT it can still affect the INR:
*** MUI IMPORTANTE ***
Argatroban.
Lepirudin has little effect on INR (Both drugs are monitored looking at aPTT)
Which anticoagulants are not to be used in HIT and why?
Warfarin - don't use as monotherapy
LMWH - May crossreact with heparin antibodies.
When, if ever, can a patient with a hx of HIT, be re-exposed to heparin?
Ab negative
Remote hx of HIT
No comparative txt
Ltd exposure to heparin
What is the active component that breaks down clots?
Plasminogen --> activated to --> Plasmin
What are the targets of plasmin
Fibrin
Factor V
Factor VIII
How can you block activation of plasminogen?
alpha-2anti-plasmin - blocks active enzyme
Plasminogen activator inhibitor - block conversion to active enzyme
Name two plasminogen activators found in our bodies:
tpa - Tissue plasminogen activator
Urokinase plasminogen activator
Name two plasminogen activators available therapeutically:
Streptokinase - not used though because tends to be immunogenic
Contact system
Main disadvantage of clot busters?
If given systemically, likely to cause hemorrhage.
What is the rationale for the use of anticoagulant medications:
Prevent propagation of clots (Rx)
Prevent formation of new clots (prophylaxis)
Prevent formation of recurrent clots (secondary prophylaxis)
Heparin:
What is the MOA?
How is it eliminated?
Half life?
How would you reverse the effects of heparin?
How is Heparin monitored?
Binds to antithrombin III --> inhibit factors Xa and IIa

Eliminated via the reticuloendothelial system.
Heparin is monitored by measuring the aPTT - intrinsic pathway.
Has a half life of 1 - 1.5hrs
Reverse effects by administering protamine sulfate
List four LMWH drugs - generic names:
Enoxaparin
Dalteparin
Tinzaparin
Fondaparinux - longer half life than the others = 17 - 21hrs
LMWH:
hat is the MOA?
How is it eliminated?
Half life?
How would you reverse the effects of heparin?
How is LMWH monitored?
MOA: Antithrombin III - inhibit Xa and IIa
Elimination: RENAL ***
Half life = 2.5 - 4.5hrs
Reverse = ONLY 60% REVERSAL IS ACHIEVED WITH PROTAMINE SULFATE, except Fondaparinux has no reversal agent at this time.
Monitoring: No monitoring is necessary
Difference between the route of administration of heparin vs that of LMWH:
Heparin is administered IV whereas LMWH is given subcutaneously.
Warfarin:
What is the MOA?
MOA: Inactivates Vitamin K Reductase. Hence do not have the reduced form of vitamin K that is needed for carboxylation o glutamic acid residues to form gamma carboxylation of ***Factors II, VII, IX, X, protein C and protein S ***
Warfarin:
How is it eliminated?
Half life?
How would you reverse the effects of warfarin?
How is warfarin monitored?
Elimination: Hepatic metabolism and unleashed via urine and stool. ALWAYS THINK OF DRUG INTERACTIONS WITH WARFARIN.
Half life: 40hrs
Reverse effects: Vitamin K, Fresh Frozen plasma, Profilnine
Monitored: INR
How long does it take for all coagulation factors (II, VII, IX and X) to be inhibited by warfarin?
5 days, patients are given warfarin as prophylaxis and prevention of recurrent clots. For the first five days, they will be on both heparin and warfarin until the effect of warfarin kicks in.
Name some of the clinical applications of anticoagulant medications:
Prevent DVT and PE after surgery
Prevent DVT and PE in hospitalized medically ill patients
Treat acute DVT or PE
Treat Embolic stroke
Treat atrial fibrillation
Treat patients with mechanical prosthetic hearts
Acute coronary syndrome
Describe HIT Type 1 syndrome:
Heparin associated thrombocytopenia which is transient, mild, non-immunologic and occurs within 4 days of exposure. It is rapidly reversible and asymptomatic.
Why is the use of warfarin monotherapy without a systemic anticoagulant contraindicated?
Warfarin on its own may exacerbate venous gangrene
What is the aim of laboratory diagnosis in Rx of HIT?
Need tests that can determine the antibody responsible for platelet activation and aggregation.
How is the Serotonin Release
Assay test performed in Dx of HIT?
Patients serum is mixed with donor platelets that were incubated with radioactive serotonin. Normally, serotonin is released by activated platelets in presence of heparin
What is the major disadvantage of Heparin alternative drugs that may be used in HIT patients?
They do not have reversal agents if bleeding was to occur.
What are the indications for use of thrombolytic therapy?
MI within 6hrs
Peripheral arterial or graft occlusion ( usually by catheter delivery)
Cerebrovascular accident if given within 3hrs of first symptoms
PE
DVT
Contraindications for thromboembolytic therapy use:
Surgery within 10 days
Trauma within 10 days
Serious GI bleed within the past 3 months
Hx of htn
Active bleed or hemorrhagic disorder.
Previous cerebrovascular or intravascular process
Aortic dissection
Acute pericarditis
TRUE OR FALSE
All thromboembolytic drugs require follow up treatment with an antithrombotic or anticoagulant agent.
TRUE